Correlation Between Genotyping And Perfusion CT Parameters And Prognosis Of Patients With Glioma

Objective: Glioma is a systemic brain disease with a high degree of malignancy,short survival time,and the spread of tumor cells far beyond the macroscopic visible range of lesions,forming a network of connections in the whole brain.The WHO grading system classifies gliomas into grades I-IV,and grade IV gliomas have the worst prognosis.A large number of studies have shown that there is a close relationship between local blood flow changes and WHO grade of glioma.However,with the discovery and research of glioma gene targets in recent years,the subtypes of glioma have been re-stratified.Based on molecular pathological diagnosis of gliomas,previous studies have shown that tumor genetic markers independently or interactively influence the degree of glioma malignancy(e.g.IDH gene mutation status MGMT gene promoter methylation status and TERT gene mutation status),but there is no correlation study between local blood flow changes in glioma and tumor genotyping.The purpose of this study was to investigate the relationship between brain blood volume(CBV),brain blood flow(CBF),mean transit time(MTT),time to peak(TTP)and tumor permeability surface(PS)values and tumor biological characteristics in patients with glioma.To further search for more accurate clinical biological markers of glioma,and try to understand the mechanism of blood perfusion changes in glioma of different malignant degrees,so as to provide a basis for clinical diagnosis and treatment of glioma patients.Methods: A retrospective analysis was performed on preoperative perfusion CT of 46 patients diagnosed with glioma who were admitted to the Neurosurgery Department of The Affiliated Hospital of Southwest Medical University from January 2018 to November 2018.All the included patients received surgical treatment and had a clear pathological diagnosis of glioma.Regions of interest ROI method was used to measure the local blood flow parameters of the samples,and the samples were classified according to the latest WHO classification standard.Finally,the correlation and difference analysis were used to compare each group.Results: Among 46 patients with glioma,there were 21 patients with IDH gene mutation(45.7%),25 patients with IDH gene wild-type(63%),29 patients with TERT gene mutation(63%),17 patients with TERT gene wildtype(37%),33 patients with MGMT promoter methylation(71.7%),and 25 patients with IDH gene wild-type(63%).Non-methylation of MGMT in 13cases(28.3%).According to the mutation status of IDH gene and TERT gene,44 patients with diffuse glioma in WHO grade II-IV were divided into4 subgroups,group A was IDH gene wild type and TERT gene mutant,group B was IDH gene wild type and TERT gene wild type.The proportion of patients with glioblastoma(GBM)in group A and GROUP B was the highest,accounting for 66.7% and 62.5%,respectively.Group C had IDH gene mutation and TERT gene mutation,mainly oligodendroglioma(OL)and anaplastic oligodendroglioma(AO),accounting for 85.8%.Group D had IDH gene mutation and TERT gene wild Type I,mainly diffuse astroglioma(DA),accounted for 71.4.In the correlation analysis,according to WHO pathological grade,the relative cerebral blood volume(r CBV),relative mean flow passing practice(r MTT)and relative surface permeability(r PS)of patients showed an increasing trend with the increase of tumor grade.According to the comparison of perfusion parameters of different tumor biological markers,there were significant differences in blood perfusion parameters among different gene subtypes.The relative cerebral blood volume(r CBV)and relative surface permeability(r PS)in perfusion CT of IDH gene mutant group and IDH gene wild type group were different.r CBV: IDH mutant vs IDH wild-type group: t/Z=-3.38,P=?0.002;r PS: IDH mutant group vs IDH wild-type group: t/Z=3.25,P=?0.001;MGMT gene methylated group vs MGMT gene unmethylated group: r CBF: t /Z=1.99,P =?0.047;MVD: t /Z=2.209,P =?0.033;There were no statistical difference between BRAF gene mutant group and wild type group in CT parameters and MVD values of perfusion.In addition,ki-67 gene was associated with relative cerebral blood volume(r CBV).According to WHO pathological grading and genotyping,the IDH/TERT gene combined classification of WHO II-IV glioma was divided into four groups,and the mean r CBV of each group was different(P<0.05),while r PS value was close to statistical significance(P=0.057).According to the comparison of progression-free survival(FPS)and overall survival(OS)in each group,there were differences in FPS and OS among the four groups(P<0.05),among which,the IDH wild-type/TERTmut group had the highest relative cerebral blood volume(r CBV)and the shortest progression-free survival(FPS)and overall survival(OS),while the IDHmut/TERTmut group had the longest progression-free survival(FPS)and overall survival(OS).However,The IDHmut/TERT wild-type group had lower relative cerebral blood volume(r CBV)and higher relative surface permeability(r PS)than the IDHmut/TERTmut group.In all pathological level for four glioblastoma,MGMT/TERT gene combination classified as four categories,the perfusion parameters and progression-free survival and overall survival compared differences,there was no statistically significant difference between groups of perfusion parameters.However,there were differences in progression-free survival(FPS)and overall survival(OS)among all groups(P < 0.05),and the progression-free survival(FPS)and overall survival(OS)in MGMTunmethylated/TERTmut group were the shortest.Cox regression analysis showed that radiotherapy and chemotherapy was a protective factor for postoperative recurrence of grade II-IV glioma patients(HR=0.240,95%CI: 0.081-0.717).WHO grade IV was a risk factor for postoperative recurrence compared with grade II(HR=6.658,95%CI: 1.179-37.590).The genotypes were IDH wild-type/TERT wild-type(HR=0.180,95%CI: 0.050-0.652)and IDH mut/TERTmut(HR=0.108,95%CI: 0.027-0.426)was a protective factor for postoperative recurrence compared with IDH wildtype/TERTmut.Prior chemoradiotherapy was a protective factor for survival in grade II-IV glioma patients(HR=0.233,95%CI: 0.059-0.851).WHO grade IV versus grade II was a risk factor for survival(HR=17.061,95%CI: 2.260-128.817).Genotypes were IDH wildtype/TERT wild-type(HR=0.109,95%CI: 0.023-0.516)and IDHmut/TERTmut(HR=0.106,95%CI:0.021-0.531)was a protective factor for survival compared with IDH wild-type /TERTmut.Genotypes were MGMT methylated/TERT wild-type(HR=0.011,95%CI: 0.000-0.378)and MGMT methylated/TERTmut(HR=0.016,95%CI:0.001-0.209)and MGMT unmethylated/TERT wild-type(HR=0.015,95%CI: 0.001-0.223)were protective factors for postoperative recurrence in patients with glioblastoma compared with MGMT unmethylated/TERTmut.Genotypes were MGMT methylated/TERT wild-type(HR=0.042,95%CI: 0.003-0.673)and MGMT methylated/TERTmut(HR=0.033,95%CI:0.004-0.297)and MGMT unmethylated/TERT wild-type(HR=0.045,95%CI: 0.005-0.395)were protective factors for postoperative recurrence in patients with glioblastoma compared with MGMT unmethylated/TERT wild-type.Conclusion: CT perfusion parameters and prognosis of glioma patients with different genotypes are significantly different.